1 5-substituted indazoles

ABSTRACT

1,5-SUBSTITUTED INDAZOLES HAVING THE STRUCTURAL FORMULA   1-X,3-Z,5-Y-1H-INDAZOLE   WHEREIN X REPRESENTS-CH2X&#39;&#39;,   -CH2-OOC-CH2-X&#39;&#39;, CH2-OOC-S-R, -CO-CH2-X&#39;&#39;, -CO-S-R,   -CO-R, -CO-NH-R, -CH2-S-C(=NH)-H3N(+) CL(-), -CH2-CH2-X&#39;&#39;   -S-C(-X&#39;&#39;)3 OR -P(=O)(-O-R)2   X&#39;&#39; REPRESENTS-OH,-OR,-SCN, HALOGEN, OR PIPERIDINO; R REPRESENTS AN ALKYL, HALOALKYL, PHENYL, OR SUBSTITUTED PHENYL GROUP; Y REPRESENTS CHLORINE, NITRO, OR AMINO; AND Z REPRESENTS HYDROGEN OR HALOGEN, ARE USED TO CONTROL THE GROWTH OF UNDESIRABLE FUNGI, PLANTS, AND INSECTS. AMONG THE MOST ACTIVE OF THESE COMPOUNDS AS PESTICIDES ARE N&#39;&#39;-HYDROXYMETHYL-5-CHLOROINDAZOLE, 2-(5CHLOROINDAZOLYLMETHYL) THIOUREA HYDROCHLORIDE, N&#39;&#39;-THIOCYANATOMETHYL-5-NITROINDAZOLE, AND N&#39;&#39;-TRICHLOROMETHYLMERCAPTO-3,5-DICHLOROINDAZOLE.

United States Patent Int. Cl. C07d 49/18 U.S. Cl. 260-310 v x ClaimsABSTRACT or THE DISCLOSURE Li substitu ted indazoles having thestructural formula ll N .N wherein X represents CH X,

I 0 i (I) 3 0 0 0 -oH20&'0H X', --GH odSR, JOH X', QISR, HIR, NHR, -CHSC(=NH)NH +C1, CH CH X SCX ,-or

Q ll P=(OR)2 X represents -OH, OR, 'SCN, halogen, or piperidino; Rrepresents an alkyl, haloalkyl, phenyl, or substituted phenyl group; Yrepresents chlorine, nitro, or amino; and Z represents hydrogen orhalogen, are used to control the growth of undesirable fungi, plants,and insects. Among the most active of these compounds as pesticides areN-hydroxymethyl-S-chloroindazole, 2-(5- chloroindazolylmethyl) thiourea'hydrochloride, N'-thiocyanatomethyl-S-nitroindazole, and Ntrichloromethylmercapto-3,5 dichloroindazo1e.

This invention relates to novel biocidal compounds and to their use inthe control of various plant and animal pestsilt/lore particularly, itrelates to the control of the growth 0f undesirable fungi, plants, andinsects using pesticidal compositions that contain certain1,5-substituted indazoles as their biocidally-active ingredients.

In accordance with this invention, it has been discovered thatcertain-1,5-substituted indazoles have unusual and valuable activity as.fungicides, insecticides, and selective herbicides, These compounds maybe represented by the structural formula g Y sol Z It 2N wherein Xrepresents CH X',

. i =(OR)2or'P =(OR)2 Xrepresents 1'O H, OR,v --SCN, -Cl, Br, .,F, -,I,or pipericlino; R represents an alkyl group having 1 to carbon atoms, a.haloalkyl group having 1 to 4 carbon atoms, phenyl, chlorophenyl,hydroxyphenyl, alkylphenyl, or nitrophenyl; Y represents chlorine,nitro, or

amino; and Z represents hydrogen, chlorine, bromine, fluorine, oriodine. The preferred compounds for use in pesticidal compositions arethose in which Y is chlorine or nitro and Z is hydrogen or chlorine.

Illustrative of the pesticidal compounds of this invention are thefollowing:

N -hydroxymethyl-5 -chloroindazole, N'-trichloromethylmercapto-S-chloroindazo1e, N'-carbothiolethoxy-S-chloroindazole,N-thiocyanatomethyl-S-chloroindazole,

N'- N-n-butylcarbamoyl -5-chloroindazole,

N- (3 ,4-dichlorobenzoyl) -5-chloroindazole,

'N'- 5-chloroindazolyl methylethylthiol carbamate,N-chloroacetoxymethyl-S-chloroindazole,N-piperidinomethyl-S-chloroindazole, 2- (S-chloroindazolylmethylthiourea hydrochloride, N- Z-hydroxyethyl) -5-chloroindazole,

diethyl N'- S-chloroindazolyl) amido phosphate,N'-hydroxymethyl-S-nitroindazole, N'-carbothiolethoxy-S-nitroindazole,N-trich1oromethylmercapto-S-nitroind azole,

N- 3-nitro'benzoyl -5-nitroindazole, N-thiocyanatomethyl-5-nitroindazo1e, (N-5-nitroindazolyl)methylethylthiol carbonate,N'-trichloromethylmercapto-3,S-dichloroindazole, N- (4-hydroxybenzoyl)-3,5-dichloroindazole, N-hydroxymethyl-3,S-dichloroindazole,N-trichloromethylmercapto-3-chloro-5-nitroindazole,Nhydroxymethyl-3-chloro-5 -nitroindazole, N-chloroacetoxy-3-chloro-5-nitroindazole, I

N'- Z-hydroxyethyl) -3-chloro-5-nitroindazole,

and the like.

A single 1,5-substituted indazole or a mixture of two or more of thesecompounds may be present in the pesticidal compositions of thisinvention.

The substituted indazoles of this invention may be prepared by anysuitable and convenient procedure. For example, a S-Substituted indazoleor a 3-halo-5-substituted indazole may be heated as such or as itsN'-amine salt with a compound that will react with it to form thedesired 1,5-substituted indazole. Thus, S-chloroindazole or 3-chloro-S-nitroindazole may be heated with paraformaldehyde to form thecorresponding N'-hydroxymethyl compounds or with trichloromethylsulfenylchloride to form the corresponding N'-trichloromethylmercapto compounds.The reaction is generally carried out in a solvent, such as benzene,toluene, xylene, acetone, pyridine, ethanol, or ethylene dichloride, atthe reflux temperature of the reaction mixture.

The biocidal compositions of this invention may be applied to a Widevariety of fungi, plants, insects, and other pests to control or inhibittheir growth. While each of the substituted indazoles has been found tobe useful in the control of the growth of at least one of theaforementioned types of organisms, the particular pest upon which eachexerts its major effect is largely dependent upon the substituents onthe rings. For example, N'-(2- hydroxyethyl)-S-chloroindazole is mosteffective as a selective herbicide, While N'-thiocyanatomethylS-nitroindazole is most effective as a foliar fungicide and N'-piperidinomethyl-5-chloroindazole as a soil fungicide.

The locus in which pest control is to be effected may, if desired, betreated with the compounds of this invention. Alternatively, thecompounds may be applied directly to the undesirable organisms tocontrol or inhibit their growth. a

While the 1,5-substituted indazoles may be used as such in the processesof this invention, they are usually and preferably used in combinationwith an inert carrier that facilitates the dispensing of dosagequantities of the pesticide and assists in its absorption by 'theorganism whose growth is to be controlled. The pesticidal compounds maybe mixed with or deposited upon inert particulate solids, such asfullers earth, talc, diatomaceous earth, hydrated calcium silicate,kaolin, and the like, to

4 ml. of benzene which was being heated at its reflux temperature wasadded over a period of 45 minutes 39.8 grams (0.2 mole) oftrichloromethanesulfenyl chloride and 250 ml. of benzene. The resultingmixture was heated form dry particulate compositions. Such compositionsat its reflux temperature for 1.25 hours, cooled to room may, ifdesired, be dispersed in water with or without the temperature, andfiltered. The filtrate was washed with aid of a surface-active agent.The pesticidal compounds two 100 ml. portions of water and then heatedto remove are preferably dispensed in the form of solutions or disthebenzene. There was obtained a 58 percent yield of N persions in inertorganic solvents, water, or mixtures oftrlchloromethylmercapto-5-chloro1ndazole WhlCh melted inert organicsolvents and Water or as oil-in-water emulat 8Z-88 C. and which contamed9.0 percent N, 45.8 sions. The concentration of the pesticide in thecompercent CI, and 9.2 percent S (calculated, 8.7 percent N, positionsmay vary within wide limits and depends upon 47.0 percent Cl, and 10.6percent S). a number of factors, the most important of Whlgh are theEXAMPLE 3 t e or t es of organisms being treated and t e rate at vi liich th omposition is to be applied. In most cases the To a mIXture 0fgrams 9 Of composition contains approximately 0.1 percent to 85perlHdaZOle, grams (9' mole) of tflethylalqlne, and cent by weight ofone or more of the aforementioned sub- 300 of benzene Whlch had heated{0 mflux stit-uted indazoles. If desired, the compositions may alsotemperature Was addcd OVET Perlod of one hour 255 contain otherfungicides, such as sulfur, the metal digrams of ethyl 31101 fofmate andof methyl dithiocarbamates, and the metal ethylene bis- 2 benzene. Themixture was heated at its reflux temperature (dithiocarbamates);insecticides, such as chlordane, benfor 3 hours, cooled to TOQIIITemperature, fi zene hexachloride, and DDT; or plant nutrients, such asThe filtrate was Washed Wlth two 100 Portlons of urea, ammonium nitrate,and potash. Water and then heated to remove the benzene. The prod- Theamount of the composition used is that which will l'ecl'ystalllled mPetroleum efheli The N bring about satisfactory control of the growth ofthe or- 25 carbothlolethoxy obtamed melted at ganism. To achieve controlof fungi and insects, for ex- 12950-1305 and Contalned Percent C, Pample, an amount of the composition that is used is that cent H, andPercent N (Calculated, Percent C, which will apply to the locus or tothe organism about 50 Percent and p.p.m. to 10,000 p.p.m. of the activecompound since EXAMPILB4 these amounts will ordinarily control the pestwithout injuring plants. Herbicidal compositions are generally used 5 it 8 g 2:gg in amounts that will apply about 1 pound to 20 pounds of 0mmam grams m0 o t3: g g; 15 further Illustrated by the examples theacetone. The N'-thiocyanatomethyl-5-cl1l0roindazole EXAMPLE 1 obtainedmelted at 135-145 C. and contained 16.9 per- A t f grams (0 296 ole) of5 chlowin cent N (calculated, 17.9 percent N).

mix ure 0 m dazole, 11.1 grams (0.369 mole) of paraformaldehyde, EXAMPLE5-30 200 ml. of ethanol, and 2.3 ml. of 5% aqueous sodium 40 Thefollowing 1,5-snbstituted indazoles were prepared hydroxide solution washeated at its reflux temperature by the procedures set forth in Examples14.

Analysis (percent) Melting Calculated Found Example No. Compound rangeC.) C H N 5 N-(N-n-butylearbamoy1)-5-ch1oroindazole 57.2 5.6 16.7 6N-(3,4dlch1orobenzyo1)-5-chloroindazole 182.5183.5 51.6 2.2 8.6 7N-(5-chl0roindazolyl)-methyethylthiol carbonate 48.9 4.1 10.6 8N-chloroacetoxymethyl-5-chloroindazole.- 46.3 3.1 10.8N-piperidinomethyl-E-chlorolndazole 16. 12(fiehloroindazolylmethyl)thioureaHCl. 20. 3

N -trlchloromethylmercapto-5-nltroindazole N-(3,4-dlehlorophenylcarbamoyl)-5-ehloroindazole N-(2 hydroxyethyl) -5-ehlorolndazole Dlethyl N-(5-ehloroindazoly1)amldo ph0sphate N-chloroacetyl-5-chloroindaz oleN"hydroxymethyl-fi-mtrolndazole N'-earbothlolethoxy-G-nitroindazoleN-piperidinomethyl-B-nitroindazole N-thioeyanatomethyl-5-nitrolndazole(N-5-nitrolndazolyl)methylethylthlol earbonate2-(fi-nltroindazolylmethyl) thiourea.HClN-trlchloromethylmercapto-3,5-diehloroindazole N-hydroxymethyl-3,5-dieh1oroindazole N (3 ,4-dlehlorob enzoyl)-3,5-d1ehloroindazole N-triehloromethylmercapto-3eh1oro-5-nltroindazoleN-earbothlolethoxy-3-chloro-5-nitroindaz0le.-N-hydroxymethyl-3-chloro-5-nitroindazole.

28 i N-ehloroaeetoxy-3-ehloro-5-n1trolndazole 29.- N'-(2-hydroxyethyl)-3ehloro-6-nltroindaz0le 30 N- (3,4-dichlorobenzoyl)-3-ehloro-5-nltroindazole m aw r s i ew IPNQCDH 1 011. 8 Dee.

for 2.75 hours, cooled, and filtered. The solid product was washed withethanol and dried. There was obtained a 73 percent yield ofN'-hydroxymethyl-5-chloroindazole,

which melted at 126126.5 C. and which contained 19.1

percent Cl and 15.3 percent N (calculated, 19.4 percent Cl and 15.1percent N). 1 j

EXAMPLE 2 To a mixture of 30.5 grams (0.2 mole) of 5-chloroindazole, 22grams (0.2 mole) of triethylamine, and 250 EXAMPLE 31 Acetone solutionswere prepared by dissolving 100 mg. portions of the products of Examples1-30 in 10 ml. of acetone that contained 2.000 ppm. of sorbitantrioleate and 5000 ppm. of a polyoxyethylene ether of sorbitanmonooleate. The acetone solutions were dispersed. in ml. portions ofdistilled water to form aqueous solutions that contained 1000 ppm. ofthe 1,5-substituted indazole. More dilute solutions were prepared byadding distilled water to these solutions.

1 l EXAMPLE 3:. A series of tests was carried out in which the1,5-substltuted indazoles were evaluated as selective herbicides.

6 v disease was noted. In no case was there appreciable'injury to theplants. The results obtained are summarized in Table III.

TABLE r-ac'r-rvr'rx OF 1,5-SUBSTITUTED INDAZOLES AS SELECTIVE HnRBrorDEsRate Soy Sugar Mornin Buck- R e Crab- Herbicide, product of--(lbs./acre) Clover bean beet Cotton Corn Oats Mustard glorg wheat grazegrass Foxtail Example 1 10 w 3 5 4 3 2 2 5 4 4 1 1 1 Example 4 4 g g 4 g2 4 2 2 2 0 4 3 4 4 3 4 4 5 3 Exampl 1o a 2 3 2 2 a 3 2 a 1 a a Example8j 28 g g g g g 2 4 2 3 1 2 -1 4 5 4 4 4 5 4 Example 11 g g g :2 g g s a2 2 4 2 5 5 5 3 4 4: Example 3 4 2 a 2 1 1 2 3 2 1 s 1 Example 16 10 5 43 1 2 1 5 5 4 4 1 1 2 s 2 2 2 5, s 2 2 2 2 1 Example 18 10 3 2 5 2 2 2 42 2 2 2 1 I I 5 3 2 4 1 2 1 3 1 1 1 ,1 1 20 4' 3 5 4 2 1 4 .4 4 I 1 1Example 27 10 ,3 2 3 3 2 1 4 2 1 1 1 1 .2 a 2 a a 1 1 1 1 1 1 1 4 2 2 12 1 Example 28 The tests were carried out by spraying seedlings ofvarious plant species with solutions prepared according to the processof Example 31 and observing the results 43 days after this treatment.

In Table I a numerical scale is used to show the herbicidal activity ofthe test compounds. On this scale, 1 indicates no injury to the plants;2 indicates slight injury; 3 indicates moderate injury; 4 indicatessevere injury; and 5 indicates that all of the plants were killed.

EXAMPLE 33 Separate lots of sterilized soil were inoculated with plantpathogens. The inoculated soil was placed in 4-ounce containers, and thesoil in each container was drenched with m1. of an aqueous suspensioncontaining a fungicidal solution prepared by the process of Example 31.After incubation for two days at 70 F., the amount of mycelial growth onthe surface of the soil was noted. The results of these tests are givenin Table II. In this table, a rating of 1 indicates growth equal to thatin inoculated soil that had not been treated with a fungicide; 2indicates 4 that about 75% of the surface was covered with colonies ofthe organism; 3 indicates that about half of the surface was coveredwith colonies of the organism; 4 indicates that a few scattered colonieswere present; and 5 indicates that there was no growth on the surface ofthe soil.

TABLE IIL-ACTIVITY OE 1,5-SUBS'IITUTED INDAZOLES AS FOLIAR FUNGICIDESPercent control of- Late blight of tomatoes Rate (up- Early blight oftomatoes Fungiclde, product of- Example 3 1, 000 1,000 Example 4 0Example 10 Example 15.--- Example 18 Example 19 Example 22 .4 Example 24Example 25 Example 26 Example 29 Example 30 TABLE IL-AOIIVITY OF1,5-SUBSTITUTED INDAZOLES AS SOIL FUN GICID E S Plant pathogen RateSclerotimrr Pythium Rhizortom'a Fusarium Fungicide, product of-(lbs/acre) 102 m sp. solanl oxyspomm Example 6 300 5 5 3 3 Example 7.300 5 4 2 1 Example 8. g 4 5 5 Example 9 150 2 g 3 i Example 13 300 5 44 2 Example 18 g g g 1 Example 22 150 1 2 1 3 Example 25- 300 3 3 3 2Example 27 300 4 3 3 4 EXAMPLE 34 The terms and expressions which havebeen employed are used as terms of description and not of limitation.There is no intention in the use of such terms and expressions ofexcluding any equivalents of the features shown and described orportions thereof; it is recognized, however, that various modificationsare possible within the scope of the invention claimed.

What is claimed is:

wherein X represents halogen and Z represents hydrogen or halogen.

2. A compound as set forth in claim 1 wherein X is chlorine and Z ishydrogen.

3. A compound as set forth in claim 1 wherein X is chlorine and Z ischlorine.

4. An indazole of the formula wherein X is halogen of atomic number from17 to 35.

5. The indazole of the formula til Cl (III-Cl l S-CCla References CitedUNITED STATES PATENTS 5/ 1951 Kittleson 260309.5 5/1951 Hawley et a1.260309;5 7/1958 Kuhle et a1. 424'273 5/1959 Cannon 260''3 10R 4/ 1965Kohn 260-'-309.5

OTHER REFERENCES Schlager Chem. Abst., vol. 61, column 700, 3 (19 64),

20 QD1.A51.

NATALIE TROUSOF, Primary Examiner U.S. c1. XJR.

' UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION 3,641,050 DatedFeb. 8, 1972 Patent No.

Inventor(s) Pasquale P. Minieri It is certified that error appears inthe above-identified patent and that said Letters Patent are herebycorrected as shown below:

II Column 1, lines 66 and 67, delete P=== (0R) first occurrence.

Column 5, line 58, change "Pythium" to P thium Signed and sealed this30th day of April 197A.

(SEAL) Attest:

EDWARD M.PLETCHEH,JR. C. MARSHALL DANN Attesting Officer Commissioner ofPatents USCOMM-DF 60376-P69 u.s. GOVERNMENT PRINTING OFFICE was0-366-334 FORM PO-1050 (10-69) UNITED STATES PATENT OFFICE 3,641,050Dated Patent No.

Inventor(s) Pasquale P. Minieri Occurrence (SEAL) Attest:

EDWARD PLFLETCHEILJR. Attesting Officer- CERTIFICATE OF CORRECTION VFeb. 8, 1972 It is certified that error appears in the above-identifiedpatent and that said Letters Patent are hereby corrected as shown below:

ll Column 1, lines 66 and 67, delete -P=== (OR) flrst Column 5, line 58,change "Pythium" to -Pzthium Signed and Y sealed this 30th day of April19m.

C. MARSHALL DANN Commissioner of Patents FORM PO-1050 (10-69) USCOMM-D60376-P69 a use covznnmsm mm'rms o lcz an oaes-szu

